Laser microprobe analysis of brain aluminum in Alzheimer's disease

Aluminum (Al) levels were measured in the cytoplasm and nucleus of 241 neurofibrillary tangle (NFT)-bearing neurons, in 217 NFT-free neurons and adjacent neuropil from 7 autopsy-confirmed Alzheimer's disease (AD) patients, and in 316 normal neurons from 5 control subjects, by laser microprobe mass spectrometry. Grand mean Al levels (dry weight basis) in AD samples were 2.93 +/- 1.24 micrograms/gm for NFT-bearing neuron cytoplasm, 3.54 +/- 1.39 micrograms/gm for NFT-bearing neuron nuclei, 2.31 +/- 1.09 micrograms/gm for NFT-free neuron cytoplasm, and 3.23 +/- 1.09 micrograms/gm for NFT-free neuron nuclei. Control values were 1.85 +/- 0.78 micrograms/gm for cytoplasm and 2.01 +/- 0.93 micrograms/gm for nuclei. The differences between corresponding regions of AD NFT-bearing, AD NFT-free, and control neurons were not significant (p > 0.05, analysis of variance). Al levels in neuropil were identical for AD and control samples at 2.16 +/- 0.93 micrograms/gm. In contrast to some literature reports, we found very few (< 2.5%) extremely high Al values (> 20 micrograms/gm, dry weight) on a cellular basis in AD samples. AD neurons did exhibit a higher number of Al values (9.6-14.3%) that were > 3 sigma above the corresponding control means, than did control neurons (1.3-1.6%), indicating that small elevations of Al may exist in patients with AD. Our data suggest that any Al accumulation in patients with AD is small and generalized in both NFT-free and NFT-bearing neurons and that analyses of large bulk brain samples are likely to have AD/control differences masked by the large amount of unaffected neuropil sampled.